1. Field of the Invention
The present invention relates generally to the field of peptide chemistry and, more specifically, to novel opioid peptides that can inhibit ligand binding to an opioid receptor.
2. Background Information
There are at least three known subtypes of opioid receptors, mu (.mu.), delta (.delta.), and kappa (.kappa.), to which morphine, the enkephalins, and the dynorphins, respectively, bind. The three receptor subtypes possess analgesic properties. However, the type of pain inhibited and the secondary functions vary with each receptor type. The .mu. receptor is generally regarded as the one associated with pain relief, respiratory depression, intestinal motility, antidiuresis, an immune response, and drug or other physical dependence. The .delta. receptor, on the other hand, is associated with thermal analgesia and, to a lesser extent, respiration and addiction. The .kappa. receptor, though associated with dysphoric and psychometric effects, also has a lower potential for dependence as compared to the .mu. receptor. The .kappa. receptor is potent in affecting analgesia in response to pain, including chemical stimuli. The .kappa. receptor also induces diuresis and sedation. These differences in the opioid receptor functions encourage the search for drugs which produce analgesia without deleterious side effects.
The use of synthetic peptides has been instrumental in the delineation of these subtypes and in providing analogues that can be used for studying the interactions of ligands specific to these receptor systems in both in vitro and in vivo systems. Certain opioid compounds are agonists (bind to the receptor and produce an effect) while others are antagonists (bind to the receptor but do not produce an effect). Most previously known agonists and antagonists of the opioid receptors are analogues of the enkephalins and related peptides, including the dynorphins, the dermenkephalins and the casomorphins. The compounds of the present invention have little to no sequence homology with any of these known opioid peptides.
Recent advances in methods for the preparation and screening of large numbers of individual peptides has led to the identification of numerous peptides useful in all areas of biomedical research, including research regarding the interaction of a ligand to the opiate receptor. Both receptor-specific agonists and antagonists are needed as pharmacological tools and as therapeutic agents. Even with these advances, however, basic research and drug discovery has been limited by the availability of the requisite large number of diverse opiate agonists and antagonists required to ascertain the relationship between a ligand for a particular opiate receptor subtype. Thus, a need exists for large numbers of individual compounds for use in biomedical research, including those for the study of opiate ligand-receptor interactions. As well there is a need for opioid peptides which have therapeutic value. This invention satisfies these needs and provides related advantages as well.